While taste cell renewal is inhibited in both the LPS-induced acute inflammation model and the MRL/lpr autoimmune/ chronic inflammation model, the underlying mechanisms that lead to this inhibition appear to be different. In the LPS-induced acute inflammation model, inhibition of taste cell renewal is primarily due to suppression of progenitor cell proliferation, whereas in the MRL/lpr model, progenitor cell proliferation in the circumvallate epithelium is not suppressed. The reason for this difference in mechanisms is unclear. The cytokine expression profile in the taste epithelium of MRL/lpr mice is distinct from that of LPS-treated mice. The LPS-induced acute inflammatory response in the taste epithelium is dominated by TNF-a and IL-6, whereas in the taste epithelium of MRL/lpr mice, IFN-c is MLN4924 Metabolic Enzyme/Protease inhibitor highly induced and TNF-a is modestly increased, and the level of IL-6 remains unchanged compared with PLX4032 controls. Whether these differences in cytokine expression between the two models contribute to the divergence in the regulatory mechanisms will be investigated in future studies. Type II taste receptor cells are preferentially affected in MRL/ lpr mice. The number of gustducin-positive cells per taste bud is significantly reduced in these mice. In contrast, the number of NCAM-positive cells per taste bud in MRL/lpr mice is comparable to that in controls. In addition, qRT-PCR analyses show that mRNA levels of the type II taste cells markers gustducin, TrpM5, and NeuroD are decreased in MRL/lpr mice, but not mRNA levels of the type III taste cell markers SNAP25 and PKD2L1. The reduction is about 50% in the number of gustducin-positive cells per taste bud, as well as in the mRNA levels of type II cell markers, suggesting that the decreased number of type II cells is the primary cause for the decline in the levels of type II cell markers. Type II taste receptor cells are essential for bitter, sweet, and umami taste reception and signaling. Sour and salty tastes, on the other hand, are likely detected by type III and/or I taste cells. In line with these studies and in agreement with the observed type II cell defects, our nerve recording experiments show that MRL/lpr mice are less responsive to the bitter compound QHCl and the sweet substance saccharin, but their responses to salty and sour compounds are comparable to those of controls. Behavioral experiments also show that MRL/lpr mice are less responsive to bitter, sweet, and umami compounds, but are normal in response to salty and sour compounds. CT nerve responses to sucrose and MSG tended to be lower in MRL/lpr mice than in MRL/+/+ mice, but the difference did not reach the level of significance, probably due to low responsiveness of the CT nerve to these compounds in both mice compared with some other mouse strains.